title: Stress response and cytoskeletal proteins involved in erythrocyte membrane remodeling upon Plasmodium falciparum invasion are differentially carbonylated in G6PD A- deficiency.
abstract: Multiple glucose-6-phosphate dehydrogenase (G6PD)-deficient alleles have reached polymorphic frequencies because of the protection they confer against malaria infection. A protection mechanism based on enhanced phagocytosis of parasitized G6PD-deficient erythrocytes that are oxidatively damaged is well accepted. Although an association of this phenotype with the impairment of the antioxidant defense in G6PD deficiency has been demonstrated, the dysfunctional pathway leading to membrane damage and modified exposure of the malaria-infected red cell to the host is not known. Thus, in this study, erythrocytes from the common African variant G6PD A- were used to analyze by redox proteomics the major oxidative changes occurring in the host membrane proteins during the intraerythrocytic development of Plasmodium falciparum, the most lethal malaria parasite. Fifteen carbonylated membrane proteins exclusively identified in infected G6PD A- red blood cells revealed selective oxidation of host proteins upon malarial infection. As a result, three pathways in the host erythrocyte were oxidatively damaged in G6PD A-: (1) traffic/assembly of exported parasite proteins in red cell cytoskeleton and surface, (2) oxidative stress defense proteins, and (3) stress response proteins. Additional identification of hemichromes associated with membrane proteins also supports a role for specific oxidative modifications in protection against malaria by G6PD polymorphisms.
authors.affiliation: Departamento de Bioquímica y Biología Molecular IV, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: Méndez
authors.forename: María
authors.initials: M
authors.lastname: Linares
authors.forename: Amalia
authors.initials: A
authors.lastname: Diez
authors.forename: Antonio
authors.initials: A
authors.lastname: Puyet
authors.forename: José M
authors.initials: JM
authors.lastname: Bautista
mesh_terms: D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000469:parasitology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010963:Plasmodium falciparum / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D050050:Protein Carbonylation
chemical_list: D003598:Cytoskeletal Proteins